A few weeks ago, the economist Tyler Cowen attended a meeting in Manhattan during which Bill Gates briefed him and a small group of other guests on his latest philanthropic endeavors. Cowen was impressed. But one thing that impressed him in particular, as he later wrote on his popular blog, Marginal Revolution, was that Gates had been “smart enough, and health-savvy enough” to begin his presentation without first shaking everyone’s hand.

“He could spend his whole life shaking people’s hands, and basically be sick all the time,” Cowen said later, adding, “I shake hands with people, but I wish the whole custom didn’t exist. I’d rather bow or just pass business cards or something.”

Cowen, a professor at George Mason University, is not alone in worrying about the dangers of the handshake. He is part of a small but adamant group of people who believe that one of our most common customs—the symbol of “hello,” “goodbye,” and “let’s make a deal”—is also one of our most reckless. Other notables in the club include Donald Trump, who once called handshaking “one of the curses of American society,” and the high-profile technology investor Michael Arrington, who has written that he’d rather not “swap germs via the ancient but disgusting habit of shaking hands.”

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Handshake phobia is not just the province of eccentric boldfaced names. At last year’s Olympics, British doctors advised athletes to eschew the longstanding symbol of sportsmanship in order to avoid getting sick. And during the H1N1 epidemic of 2009, many school administrators, including at Northeastern University, decided to skip the ritualistic pressing of the flesh at graduation ceremonies, while the website stophandshaking.com began selling anti-handshake lapel pins, trumpeting the motto, “No offense. It just makes sense.”

During these winter months, as pharmacies advertise flu vaccines and bottles of Purell sprout at every checkout counter, it’s easy to imagine that the anti-handshake activists have a point. But do they? To pursue an answer to this question is to encounter a startling fact: When it comes to how much of a risk we’re taking by shaking hands, doctors and scientists can’t seem to agree.

“We don’t know,” said Allison Aiello, an associate professor of epidemiology at the University of Michigan School of Public Health, speaking specifically about the frequency of hand-to-hand transmission of flu. “As researchers, it’s the million-dollar question. We really want to know.”

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Without a doubt, experts say, it’s possible to catch cold and flu by touching other people, and regularly scrubbing your hands with soap and water is never a bad idea. But how often those diseases are actually spread through hand-to-hand contact, compared to the rate of infection through the air, is a debate that stretches back in part to two dueling —not to mention quite disgusting—studies conducted during the 1970s and ’80s, and which has never really been resolved.

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The handshake is said to have started more than 2,000 years ago as a way for people to show one another they were unarmed. Today, we use handshakes to mark introductions, agreements, and farewells—at job interviews, business meetings, and conversations at parties. Handshakes serve as a kind of social punctuation mark, a gestural way to say, “Here we are and here we go.”

But something else can happen when two people shake hands: Some of the microscopic critters on our fingers and palms trade their old digs in for new ones. Germophobes have been worried about this almost as long as germs have been known to cause disease. In 1925, Time Magazine reported on a doctor in Ann Arbor, Mich., who believed the average man’s hands were “contaminated with...secretions,” and that people who insisted on shaking hands anyway were “purveyors of death.” Around the same time, a soap industry organization called the Cleanliness Institute waged a campaign against the practice, which it called “a biological discourtesy.”

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Anti-handshake sentiment persisted through the decades. In 1996, The New York Times Magazine interviewed a professor named Robert Swindle about the festering horror of it all. “Think of all those unwashed hands,” Swindle said. “You’re talking about fungal viruses, cold viruses, warts. Who wants warts?” Soon after, the Massachusetts Medical Society aired radio ads imploring listeners to wash their hands frequently, because even a “friendly handshake can carry many illnesses.”

Through all this anxiety, the handshake has held firm. And while some, like Tyler Cowen, chalk this up to societal inertia, its enduring appeal testifies to the fact that many of us get something out of it. Studies have confirmed that the quality of our shake—the dryness of our palm, the firmness of our grip—can determine how others perceive us. Even more important, shaking hands serves as a powerful social lubricant. To not shake hands, in this light, is to opt out of harmony—to set yourself apart, and cause others to wonder whether you’re a misanthrope, a weirdo, or just plain rude.

There’s another reason, however, the custom has survived its encounter with modern science: Researchers have found it vexingly difficult to establish that touching other people’s hands is actually an important vehicle for spreading the viruses we worry about most, particularly cold and flu. The influenza virus, according to the Centers for Disease Control and Prevention, is widely believed by experts to travel mainly through the air, in the form of droplets that come out of people’s mouths and noses when they cough, sneeze, and talk. The role of hand-to-hand contact is less clear, according to Jeanette St. Pierre, a spokeswoman for the CDC, though “most people believe this type of transmission is possible.” And Arnold Monto, an epidemiologist at the University of Michigan School of Public Health, said that while “there is no direct evidence” that it spreads flu, studies have shown that using hand sanitizer does decrease the likelihood of catching it.

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Things get even murkier when it comes to the common cold, spread by rhinoviruses. Everyone agrees that the virus infects us by getting into our noses and tear ducts. But when it comes to how it gets there—specifically, the importance of hand-to-hand transfer—the best information we have comes from experiments done about 30 years ago by a pair of doctors who disagreed with each other passionately. Jack Gwaltney, now retired, was then a professor of infectious disease at the University of Virginia School of Medicine. His early experiments involved infecting a group of paid volunteers with rhinovirus by depositing it directly into their noses. Gwaltney would then have his test subjects hole up in motel rooms divided down the middle with chicken wire. On one side of the wire, he’d put a healthy volunteer, and on the other, a sick one; after 72 hours, Gwaltney’s team would run nasal tests to see if the infection had made the jump. In every case, they found, the healthy people had remained healthy—a result contrasted sharply with a separate experiment, in which healthy volunteers touched hands with sick ones before putting their fingers in their noses and eyes. Under those conditions, Gwaltney found, almost everyone in the test group got sick.

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As convincing as Gwaltney’s results were, results published around the same time by Elliot Dick at the University of Wisconsin in Madison challenged his conclusions. Dick, who died in 1996, believed Gwaltney was wrong about the spread of rhinovirus, and a series of experiments he ran during the 1980s seemed to bear that out. Perhaps the most convincing was one in which a group of test subjects, half of them infected with rhinovirus and the other half healthy, were made to sit in a room and play cards together for 12 hours straight while wearing arm braces and collars that prevented them from reaching their faces. If Gwaltney had been right, and colds happened primarily when people got the virus on their hands and then stuck it in their noses and eyes, the healthy card-players would have stayed healthy. But as it turned out, over half of them got sick. After running a control study, Dick concluded that the germs were traveling between his subjects through some other means—namely, the air.

Today, researchers who worked with Gwaltney and Dick all those years ago—and believed firmly, at the time, that their side was right—are saying that maybe the other had a point as well. “I sort of am in the position now where I think it’s probably a combination of both,” said Carlton Meschievitz, one of Dick’s coauthors, now retired. Ronald Turner, meanwhile, a former student of Gwaltney’s who is now a professor of pediatrics at the University of Virginia, said that a study he recently completed—in which the application of strong antiviral hand sanitizer was shown to have no effect on the transmission of rhinovirus—has caused him to rethink his earlier convictions.

“That era seems to have led to a lot of findings that were never followed up on,” said Meschievitz. “I’m not sure if it was because of a lack of funding, or a lack of interest, or exactly what’s happened. But for whatever reason the research [on the common cold] has decreased, to the point where I don’t see anything on it at all in recent years.”

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What, then, should we do next time we see an outstretched hand coming towards us? Of course, there’s always common sense: As Cowen put it, “If someone’s sick and you shake hands with them, there’s a real chance you’ll get sick.” But is trying to avoid this fate worth the cost of assuming that everyone actually is sick, all the time? Gwaltney, for his part, shakes hands with people without fear—he even did it with Dick “on numerous occasions,” he said—but does avoid it if someone has what looks like “a rip-roaring cold.”

The decision ends up coming down to priorities. “It’s a question of risk-benefit, when it comes down to it,” said Arnold Monto. “Are you going to risk offending your colleagues, or are you going to risk getting influenza? It’s all a question of probabilities, as is most of life.”

For powerful people like Bill Gates or Donald Trump, this might not be an issue. For those of us less immune to the effects of alienating behavior, the tradition and warmth of shaking hands may simply be worth the potential cost. In fact, until we know more, this may be part of what the handshake stands for—as not just a symbol of shared trust, but a sign of mutual optimism that what we catch from each other won’t kill us.